Anatomical Relationship Between Kallikrein-Containing Tubules and the Juxtaglomerular Apparatus in the Human Kidney

Vío, Carlos P.; Figueroa, Carlos D.; Caorsi, I

doi:10.1093/ajh/1.3.269

Cited by 55 publications

(28 citation statements)

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“…This indicates that kinins could be generated in the lumen of the CD adjacent to the site of kallikrein excretion. Additionally, the close anatomical contact between the kallikrein-containing cells and the afferent arterioles of the juxtaglomerular apparatus suggests that tissue kallikrein excreted on the basolateral side of the CNT might play some role in the regulation of the diameters of the afferent arterioles of the glomerulus (88).…”

Section: Renal Kallikreinmentioning

confidence: 99%

A Missing Link Between a High Salt Intake and Blood Pressure Increase

Katori

Murakami

2006

J Pharmacol Sci

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Abstract. It is widely accepted that a high sodium intake triggers blood pressure rise. However, only one-third of the normotensive subjects were reported to show salt-sensitivity in their blood pressure. Many factors have been proposed as causes of salt-sensitive hypertension, but none of them provides a satisfactory explanation. We propose, on the basis of accumulated data, that the reduced activity of the kallikrein-kinin system in the kidney may provide this link. Renal kallikrein is secreted by the distal connecting tubular cells and all kallikrein-kinin system components are distributed along the collecting ducts in the distal nephron. Bradykinin generated is immediately destroyed by carboxypeptidase Y-like exopeptidase and neutral endopeptidase, both quite independent from the kininases in plasma, such as angiotensin converting enzyme. The salt-sensitivity of the blood pressure depends largely upon ethnicity and potassium intake. Interestingly, potassium and ATP-sensitive potassium (K ATP ) channel blockers accelerate renal kallikrein secretion and suppress blood pressure rises in animal hypertension models. Measurement of urinary kallikrein may become necessary in salt-sensitive normotensive and hypertensive subjects. Furthermore, pharmaceutical development of renal kallikrein releasers, such as K ATP channel blockers, and renal kininase inhibitors, such as ebelactone B, may lead to the development of novel antihypertensive drugs.

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Section: Renal Kallikreinmentioning

confidence: 99%

A Missing Link Between a High Salt Intake and Blood Pressure Increase

Katori

Murakami

2006

J Pharmacol Sci

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“…17 Specific binding was detected with the biotin-streptavidin LSABϩ system (Dako). Controls included preabsorption of anti-hTK with purified human urinary TK (Calbiochem) and replacement of anti-hTK antibody by nonimmune serum at the same dilution.…”

Section: Transgene Expression After Adhtk Gene Transfermentioning

confidence: 99%

Akt/Protein Kinase B and Endothelial Nitric Oxide Synthase Mediate Muscular Neovascularization Induced by Tissue Kallikrein Gene Transfer

et al. 2004

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Background— Angiogenesis gene therapy with human tissue kallikrein (hTK) has shown promise for ischemic disease. The present study was undertaken to (1) assess an optimal gene transfer modality, (2) clarify hTK angiogenic pathways, and (3) discount possible side effects. Methods and Results— The hTK gene was transferred to murine adductors by increasing doses of an adenovirus (Ad.hTK). Heterologous protein production was evaluated by ELISA and immunohistochemistry. Structural and functional characteristics of hTK-induced neovascularization were assessed. Muscular endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF)-A mRNA and protein content were evaluated by real-time polymerase chain reaction and Western blotting. The ability of hTK to phosphorylate-activate Akt/protein kinase B (Akt-B) and VEGF receptor 2 (VEGF-R2) was also determined. Implication of the aforementioned mechanisms in Ad.hTK-induced neovascularization was challenged by blocking Akt-B with a dominant-negative Akt construct; NOS with N G -nitro- l -arginine methyl ester; and VEGF-A with neutralizing antibody, VEGF-R2 antagonist, or Ad carrying soluble VEGF-R1 gene. We found that 10 7 PFU Ad.hTK led to peak increases in capillary and arteriole density. Newly developed arterioles persisted for up to 8 weeks. Ad.hTK did not change microvascular permeability. Ad.hTK upregulated eNOS mRNA and protein and activated Akt-B through Ser-473 phosphorylation. Inhibitory studies documented that these biochemical events were instrumental to Ad.hTK-induced neovascularization. In contrast, Ad.hTK neither affected VEGF-A and VEGF-R2 levels nor increased VEGF-R2 phosphorylation. Consistently, Ad.hTK-induced neovascularization was not disturbed by any of the different approaches used to block VEGF-A. Conclusions— Our findings provide new information on the pathway involved in hTK-induced neoangiogenesis and represent an advancement toward clinical applications with Ad.hTK.

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“…We concluded that in vivo CTGF occurs and opposes the vasoconstrictor effect of TGF. afferent arteriole; macula densa; connecting tubule; glomerular filtration rate; sodium ion transport; benzamil; stop-flow pressure WE AND OTHERS HAVE SHOWN that, in the renal cortex, the connecting tubule (CNT), a segment of the nephron located between the distal convoluted tubule and collecting duct, returns to the vascular pole of the glomerulus and accompanies the afferent arteriole (Af-Art) for varying distances (2,6,7,28). This morphology is compatible with cross talk between the CNT and the Af-Art.…”

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confidence: 99%

Connecting tubule glomerular feedback antagonizes tubuloglomerular feedback in vivo

Wang

Garvin

D’Ambrosio

et al. 2010

American Journal of Physiology-Renal Physiology

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In vitro experiments showed that the connecting tubule (CNT) sends a signal that dilates the afferent arteriole (Af-Art) when Na ϩ reabsorption in the CNT lumen increases. We call this process CNT glomerular feedback (CTGF) to differentiate it from tubuloglomerular feedback (TGF), which is a cross talk between the macula densa (MD) and the Af-Art. In TGF, the MD signals the Af-Art to constrict when NaCl transport by the MD is enhanced by increased luminal NaCl. CTGF is mediated by CNT Na ϩ transport via epithelial Na ϩ channels (ENaC). However, we do not know whether CTGF occurs in vivo or whether it opposes the increase in Af-Art resistance caused by TGF. We hypothesized that CTGF occurs in vivo and opposes TGF. To test our hypothesis, we conducted in vivo micropuncture of individual rat nephrons, measuring stop-flow pressure (P SF) as an index of glomerular filtration pressure. To test whether activation of CTGF opposes TGF, we used benzamil to block CNT Na ϩ transport and thus CTGF. CTGF inhibition with the ENaC blocker benzamil (1 M) potentiated the decrease in P SF at 40 and 80 nl/min. Next, we tested whether we could augment CTGF by inhibiting NaCl reabsorption in the distal convoluted tubule with hydrochlorothiazide (HCTZ, 1 mM) to enhance NaCl delivery to the CNT. In the presence of HCTZ, benzamil potentiated the decrease in P SF at 20, 40, and 80 nl/min. We concluded that in vivo CTGF occurs and opposes the vasoconstrictor effect of TGF. afferent arteriole; macula densa; connecting tubule; glomerular filtration rate; sodium ion transport; benzamil; stop-flow pressure WE AND OTHERS HAVE SHOWN that, in the renal cortex, the connecting tubule (CNT), a segment of the nephron located between the distal convoluted tubule and collecting duct, returns to the vascular pole of the glomerulus and accompanies the afferent arteriole (Af-Art) for varying distances (2,6,7,28). This morphology is compatible with cross talk between the CNT and the Af-Art. In vitro experiments showed that the CNT sends a signal that dilates the Af-Art when Na ϩ reabsorption in the CNT increases. We called this process CNT glomerular feedback (CTGF) to differentiate it from tubuloglomerular feedback (TGF), which is cross talk between the macula densa (MD) and the 24). From a homeostatic point of view, TGF is a negative feedback loop that senses increases in NaCl at the MD and increases Af-Art resistance while at the same time decreasing glomerular filtration rate (GFR), thus favoring Na ϩ retention. On the other hand, CTGF is a positive feedback loop that decreases Af-Art resistance in response to increases in NaCl in the CNT. A decrease in Af-Art resistance increases both renal blood flow and GFR and thus favoring Na ϩ excretion. NaCl reabsorption is mediated by the thiazide-sensitive Na ϩ -Cl Ϫ cotransporter (NCC) in the distal convoluted tubule and the amiloride/ benzamil-sensitive epithelial Na ϩ channel (ENaC) in the CNT and cortical collecting duct (17,18,21). Thus benzamil blocks CTGF (23) while hydrochlorothiazide (HCTZ), by block...

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Anatomical Relationship Between Kallikrein-Containing Tubules and the Juxtaglomerular Apparatus in the Human Kidney

Cited by 55 publications

References 0 publications

A Missing Link Between a High Salt Intake and Blood Pressure Increase

A Missing Link Between a High Salt Intake and Blood Pressure Increase

Akt/Protein Kinase B and Endothelial Nitric Oxide Synthase Mediate Muscular Neovascularization Induced by Tissue Kallikrein Gene Transfer

Connecting tubule glomerular feedback antagonizes tubuloglomerular feedback in vivo

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